EP2257282A2 - Prévention et traitement de l inflammation hsmi - Google Patents

Prévention et traitement de l inflammation hsmi

Info

Publication number
EP2257282A2
EP2257282A2 EP09714090A EP09714090A EP2257282A2 EP 2257282 A2 EP2257282 A2 EP 2257282A2 EP 09714090 A EP09714090 A EP 09714090A EP 09714090 A EP09714090 A EP 09714090A EP 2257282 A2 EP2257282 A2 EP 2257282A2
Authority
EP
European Patent Office
Prior art keywords
group
atom
carbon atoms
oxygen atom
unsaturated
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP09714090A
Other languages
German (de)
English (en)
Inventor
Kjell-Arne RØRVIK
Henriette Alne
Magny Thomassen
Rolf Kristian Berge
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Thia Medica AS
Original Assignee
Thia Medica AS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Thia Medica AS filed Critical Thia Medica AS
Publication of EP2257282A2 publication Critical patent/EP2257282A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/158—Fatty acids; Fats; Products containing oils or fats
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K40/00—Shaping or working-up of animal feeding-stuffs
    • A23K40/30—Shaping or working-up of animal feeding-stuffs by encapsulating; by coating
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/80—Feeding-stuffs specially adapted for particular animals for aquatic animals, e.g. fish, crustaceans or molluscs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals

Definitions

  • the present invention relates to the use of a compound for the preparation of a nutritional and/or pharmaceutical composition for the prevention and treatment of heart and skeletal muscle inflammation (HSMI). More specifically, the present invention relates to the reduced HSMI mortality, and to an improved growth during periods with HSMI challenges.
  • HSMI heart and skeletal muscle inflammation
  • HSMI Heart and skeletal muscle inflammation
  • Affected fish may become anorexic and display abnormal swimming, but may also be slow moving without any other external signs of disease.
  • HSMI is reported to cause histopathological lesions in heart and skeletal muscle.
  • the lesions associated with HSMI is partly similar to those described for two other serious diseases in modern salmon farming; pancreas disease (PD) and cardiomyopathy syndrome (CMS), making it difficult to distinguish between them.
  • PD pancreas disease
  • CMS cardiomyopathy syndrome
  • the main difference between HSMI and PD is the absence of pancreatic lesions in HSMI. The causes and metabolic mechanisms behind these diseases are not yet solved.
  • a first aspect of the present invention thus relates to the use of a compound represented by;
  • R"-COO-(CH2)2n+i-X-R ⁇ wherein X is a sulphur atom, a selenium atom, an oxygen atom, a SO group or a SO 2 group; wherein n is an integer of 0 to 11 ; and R' is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R' contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a SO group and a SO 2 group; and R" is a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms;
  • R1 , R2, and R3 represent i) a hydrogen atom; or ii) a group having the formula CO-R in which R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or iii) a group having the formula CO-(CH 2 WrX-R', wherein X is a sulphur atom, a selenium atom, an oxygen atom, a SO group or a SO 2 group; n is an integer of 0 to 11 ; and R' is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R' contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a CH 2 group, a SO group and a SO 2
  • A1 , A2 and A3 are chosen independently and represent an oxygen atom, a sulphur atom or an N-R4 group in which R4 is a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 5 carbon atoms; wherein R1 , R2, and R3 represent i) a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 23 carbon atoms; or ii) a group having the formula CO-R in which R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or iii) a group having the formula CO-(CH 2 WrX-R', wherein X is a sulphur atom, a selenium atom, an oxygen atom, a SO group or a SO 2 group
  • HSMI heart and skeletal muscle inflammation
  • a preferred embodiement relates to the use of the compounds defined in claim 1 for improving the cardiosomatic index (CSI) of fish with HSMI or which are susceptible for HSMI.
  • CSI cardiosomatic index
  • a further aspect of the invention relates to a compound represented by;
  • R"-COO-(CH 2 ) 2n +i-X-R ⁇ wherein X is a sulphur atom, a selenium atom, an oxygen atom, a SO group or a SO 2 group; wherein n is an integer of 0 to 11 ; and R' is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R' contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a SO group and a SO 2 group; and R" is a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms;
  • R1 , R2, and R3 represent i) a hydrogen atom; or ii) a group having the formula CO-R in which R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or iii) a group having the formula CO-(CH 2 WrX-R', wherein X is a sulphur atom, a selenium atom, an oxygen atom, a SO group or a SO 2 group; n is an integer of 0 to 11 ; and R' is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R' contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a CH 2 group, a SO group and a SO 2
  • A1 , A2 and A3 are chosen independently and represent an oxygen atom, a sulphur atom or an N-R4 group in which R4 is a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 5 carbon atoms; wherein R1 , R2, and R3 represent i) a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 23 carbon atoms; or ii) a group having the formula CO-R in which R is a linear or branched alky!
  • R contains from 1 to 25 carbon atoms; or iii) a group having the formula CO-(CH 2 WrX-R', wherein X is a sulphur atom, a selenium atom, an oxygen atom, a SO group or a SO 2 group; n is an integer of 0 to 11 ; and R' is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R' contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a CH2 group, a SO group and a SO 2 group; iv) an entity selected from the group comprising -PO 3 CH 2 CHNH 3 COOH (serine), PO 3 CH 2 CH 2 NH 3 (ethanolamine), PO 3 CH 2 CH 2
  • a nutritional or pharmaceutical composition for the manufacturing of a nutritional or pharmaceutical composition, for increasing the body weight of fish with HSMI or which are susceptible for HSMI.
  • composition is administered orally.
  • composition is fed to fish, such as tilapia, Atlantic cod, Atlantic halibut, European sea bass and salmonides, preferable Atlantic salmon or rainbow trout.
  • fish such as tilapia, Atlantic cod, Atlantic halibut, European sea bass and salmonides, preferable Atlantic salmon or rainbow trout.
  • the composition is administered or fed to the fish for a period of 12 weeks, preferable 6 weeks, more preferable 3 weeks or less.
  • Preferred compounds of the present invention are non ⁇ -oxidizable fatty acid such as tetradecylthioacetic acid (TTA), tetradecylselenoacetic acid and 3-Thia-15- heptadecyne.
  • TTA tetradecylthioacetic acid
  • tetradecylselenoacetic acid 3-Thia-15- heptadecyne
  • Further preferred compounds are modified phospholipids or mono-, di- or tri- acylglycerides.
  • the composition comprises an amount of a compound defined by (a)-(c) in the range of about 0.05% to 1 ,25%, related to the weight of the feed, or more preferable 0.1 % to 0.50%, related to the weight of the feed, and more preferable about 0,25%, related to the weight of the feed.
  • compositions comprising an amount of a compound defined by an amount of a compound defined by (a)-(c) in the range of about 0.05% to 0,5%, related to the weight of the total biomass, or more preferable 0.1 % to 0.25%, related to the weight of the total biomass.
  • a further aspect of the invention relates to a fish feed containing the compounds defined in claim 1 for the prevention or treatment of heart and skeletal muscle inflammation (HSMI) of fish, and/or for reducing the mortality of fish with HSMI or which are susceptible for HSMI, and/or for increasing the body weight of fish with HSMI or which are susceptible for HSMI.
  • HSMI heart and skeletal muscle inflammation
  • a preferred embodiment of said fish feed comprises an amount of a compound defined by an amount of a compound defined by (a)-(c) in the range of about 0.05% to 0,5%, related to the weight of the total biomass, or more preferable 0.1% to 0.25%, related to the weight of the total biomass, such a about 0,25%, or more preferable about 0,50%, related to the weight of the total biomass.
  • Another preferred embodiment of said fish feed comprises an amount of a compound defined by (a)-(c) in the range of about 0.05% to 1 ,25%, related to the weight of the feed, or more preferable 0.1 % to 0.50%, related to the weight of the feed, or more preferable about 0,25%, and more preferable about 0,50% of the weight of the feed.
  • TTA tetradecylthioacetic acid
  • the compounds of the present invention are blocked in various positions and cannot be beta-oxidized. Without being bound by theory, we believe that this inhibited ⁇ -oxidation will lead to an accumulation of fatty acids in the cell, and this accumulated amount will function as a positive feedback mechanism to increase the ⁇ -oxidation of normal fatty acids.
  • Figure 1 shows the cumulative mortality during a natural outbreak of HSMI from end of May until 20 th July 2007 for farmed 0+ Atlantic salmon given four different diets, either a low-fat control diet (C1 ), high-fat control diet (C2), C2 added 0.25% TTA (E1 ) or E1 added 0.2% Carnitine (E2).
  • Figure 2 shows the total mortality during a natural HSMI outbreak in spring for the control group or the experimental group of farmed 0+ Atlantic salmon. Significant differences between dietary groups are indicated by different letters on the bars.
  • FIG. 3 shows the changes in thermal growth coefficient (TGC) and feed conversion ratio (FCR) for 0+ salmon fed the control diets or experimental diets, throughout the experimental period.
  • the four different diets were: a commercial basic diet (C1-CPK 200), C1 coated with 3% fat (2% rapeseed oil and 1 % capelin oil) (C2), C2 added 0.25% TTA (E1 ) and E1 added 0.2% carnitine (E2).
  • C1-CPK 200 C1 coated with 3% fat (2% rapeseed oil and 1 % capelin oil)
  • E1 0.25% TTA
  • E1 E1 added 0.2% carnitine
  • the experimental diets were prepared by coating the basic diet in a blender. Carnitine was dissolved in distilled water and coated onto the surface of the feed pellets for E2, to a final inclusion of 0.2%. The similar amount of water was coated onto the two other high-dietary fat diets (C2 and E1 ) and all three diets were dried at room temperature.
  • C2 was then coated with 2% rapeseed oil and E1 and E2 were coated with TTA dissolved in the same amount of rapeseed oil, to make a final dietary level of 0.25%.
  • 1 % of capelin oil was coated onto the three diets. From week seven onwards (period 2), the fish were fed the same diet as in feeding period 1 , but without added TTA. In period 2, the commercial basic diet was adjusted to a bigger fish size in accordance to the manufacturer's guidelines and the pellet size was increased (CPK 500). The two basic diets were produced by Biomar AS (Norway) (Table 1 ). All the diets were fed in excess in duplicated net pens, and feed waste sampling was performed during both feeding periods.
  • Feed conversion ratio (FCR) was calculated as (kg feed fed) x (kg final biomass-kg initial biomass + kg dead fish) "1 .
  • Cardiosomatic index (CSI) was calculated as heart weight (g) x (body weight (g)) '1 x 100.
  • Relative percent survival (RPS) was calculated as described by Ahmend (1981 ) 100% x (1 - (% mortality in the experimental group x (% mortality in the control group) "1 )).
  • TTA diets resulted in a higher final body weight (1606 ⁇ 29 grams) than control diets (1580 ⁇ 31 grams).
  • FCR feed conversion ratio
  • the mortality started at different times in the net pens, and the mortality was highest at one side of the pier. This may indicate that the disease was spread among cages and also that the cages experienced different infectious pressure during the outbreak.
  • a block design was used in our experiment, making us able to observe dietary effects even though the mortality was higher at some positions.
  • Our study was not designed to differentiate and measure infectious pressure, but the results support the suggestions made that HSMI is contagious and spread in a cage to cage pattern (Kongtorp et al., 2004a, b).
  • the heart index was found to be higher in fish fed the TTA-supplemented diets compared to the control.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Zoology (AREA)
  • Animal Husbandry (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
  • Insects & Arthropods (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Neurology (AREA)
  • Pain & Pain Management (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Marine Sciences & Fisheries (AREA)
  • Birds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Fodder In General (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne l’utilisation d’un composé dans la préparation d’une composition nutritionnelle et/ou pharmaceutique destinée à réduire la mortalité associée à l’inflammation HSMI (inflammation du cœur et des muscles squelettiques) chez le poisson.
EP09714090A 2008-02-27 2009-02-27 Prévention et traitement de l inflammation hsmi Withdrawn EP2257282A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
NO20081040A NO20081040L (no) 2008-02-27 2008-02-27 Reduced HSMI mortality
PCT/NO2009/000069 WO2009108067A2 (fr) 2008-02-27 2009-02-27 Prévention et traitement de l’inflammation hsmi

Publications (1)

Publication Number Publication Date
EP2257282A2 true EP2257282A2 (fr) 2010-12-08

Family

ID=41003478

Family Applications (1)

Application Number Title Priority Date Filing Date
EP09714090A Withdrawn EP2257282A2 (fr) 2008-02-27 2009-02-27 Prévention et traitement de l inflammation hsmi

Country Status (4)

Country Link
EP (1) EP2257282A2 (fr)
CL (1) CL2009000460A1 (fr)
NO (2) NO20081040L (fr)
WO (1) WO2009108067A2 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NO341929B1 (no) * 2009-09-14 2018-02-19 Chemoforma Ltd Fôrsammensetning
NO347765B1 (no) * 2012-11-01 2024-03-18 Ewos Innovation As Fôrsammensetning for fisk

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2570050C (fr) * 2004-06-11 2013-03-05 Pharmaq As Virus (hsmi) d'inflammation musculaire squelettique et cardiaque
KR20070046866A (ko) * 2004-07-19 2007-05-03 티아 메디카 에이에스 단백질 물질 및 비-산화성 지방산 구성요소를 포함하는조성물
NO20055541L (no) * 2005-11-23 2007-05-24 Berge Biomed As Use of fatty acid analogues

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2009108067A2 *

Also Published As

Publication number Publication date
NO20081040L (no) 2009-08-28
CL2009000460A1 (es) 2010-02-05
WO2009108067A2 (fr) 2009-09-03
WO2009108067A3 (fr) 2009-11-12
NO20101223L (no) 2010-09-02

Similar Documents

Publication Publication Date Title
Harpaz L-carnitine and its attributed functions in fish culture and nutrition—a review
Özek et al. Effects of dietary herbal essential oil mixture and organic acid preparation on laying traits, gastrointestinal tract characteristics, blood parameters and immune response of laying hens in a hot summer season
JP4995893B2 (ja) 飼料転換率を減少させるため又は腹水症の発生率を低下させるための家禽の処置
Lund et al. Effect of dietary arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid on survival, growth and pigmentation in larvae of common sole (Solea solea L.)
Kalmar et al. Dietary supplementation with dimethylglycine affects broiler performance and plasma metabolites depending on dose and dietary fatty acid profile
BR112019017258B1 (pt) Composição de ração ou aditivo de ração, seu uso e método para reduzir a produção de metano proveniente das atividades digestivas de ruminantes
Villalta et al. Effects of dietary eicosapentaenoic acid on growth, survival, pigmentation and fatty acid composition in Senegal sole (Solea senegalensis) larvae during the Artemia feeding period
Yılmaz et al. Effects of fish oil substitution with two different vegetable oil classes on fatty acid digestibility in juvenile European Sea Bass, Dicentrarchus labrax
IL258549A (en) Bird food containing capsaicinoid derivatives and methods of use for the treatment of salmonella infection
Mdhluvu et al. Crocodile meat meal as a fishmeal substitute in juvenile dusky kob (Argyrosomus japonicus) diets: Feed utilization, growth performance, blood parameters, and tissue nutrient composition
EP2257282A2 (fr) Prévention et traitement de l inflammation hsmi
BR112014020782B1 (pt) Processo de melhoria da eficiência alimentar e características das carcaças dos animais
Yao et al. Effects of dietary aqueous extract from Eucommia ulmoides Oliver on growth, muscle composition, amino acid composition and fatty acid composition of rainbow trout (Oncorhynchus mykiss)
Dokou et al. Nano-Oregano Essential Oil Improves Rainbow Trout’s () Growth Performance, Oxidative Status, Fatty Acid Profile of Fillet, Affects Gene Expression and Supports Skin and Intestinal Histomorphometry
Dibner et al. Use of Alimet® feed supplement (2-hydroxy-4-(methylthio) butanoic acid, HMTBA) for broiler production
EP1959751A2 (fr) Utilisation d'analogues d'acides gras
Gümüş et al. Effects of dietary betaine and protected calcium butyrate supplementation on growth performance, blood biochemical status, and meat quality in growing Japanese quail (Coturnix coturnix Japonica)
JP2010284087A (ja) 鶏卵、鶏卵の生産方法および改良方法、ならびに採卵鶏用飼料
Giménez Papiol et al. Effects of dietary arachidonic and eicosapentaenoic acids on common dentex (Dentex dentex Linnaeus 1758) larval performance
Shi et al. Dietary sanguinarine supplementation recovers the decrease in muscle quality and nutrient composition induced by high-fat diets of grass carp (Ctenopharyngodon idella)
Vural et al. Is royal jelly a sustainable alternative lipid source in aquaculture? Influence of dietary royal jelly levels on fatty acid composition in zebrafish
Al-Khalaifah et al. Dietary polyunsaturated fatty acids and cellular immune response in broiler chickens
US6090849A (en) Carnitine supplemented diet to prevent sudden death syndrome in breeder type poultry
Haldar et al. Copper Super‐Dosing Improves Performance of Heat‐Stressed Broiler Chickens through Modulation of Expression of Proinflammatory Cytokine Genes
Emam et al. Effect of dietary supplementation with an essential oils blend and mannan oligosaccharide on 2-the reproductive performance, egg quality and blood parameters of golden montazah layers at late phase of egg production

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20100924

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA RS

RIN1 Information on inventor provided before grant (corrected)

Inventor name: BERGE, ROLF, KRISTIAN

Inventor name: THOMASSEN, MAGNY

Inventor name: ALNE, HENRIETTE

Inventor name: RORVIK, KJELL-ARNE

17Q First examination report despatched

Effective date: 20110301

DAX Request for extension of the european patent (deleted)
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20110913